The Sigma-2 receptor is a unique protein found in most mammalian tissues. Sigma-2 receptors play an important role in growth regulation in normal cells and tumor cells of neuronal and non neuronal origin. The Sigma-2 receptor has not been purified or cloned. This grant proposal is directed at purification and cloning of the Sigma-2 receptor. This goal will be accomplished through two alternate and complementary approaches. Specific Aim 1 is entitled: Purification, Identification and Cloning of the Sigma-2 receptor using a "Click Chemistry" approach. Specific Aim 2 is entitled: Identification and cloning of the Sigma-2 receptor using an In Silico approach. Characterization of the Sigma-2 receptor is the initial step leading to a basic understanding of the role of the Sigma-2 receptor in regulation of neuronal and non-neuronal cell function and for potential therapeutic strategies to treat drugs of abuse and/or aberrant cell growth. . PUBLIC HEALTH RELEVANCE: The sigma-2 receptor is a mammalian protein in the central nervous system and in peripheral organs that may be involved in drug addiction. Sigma-2 receptors play an important role in growth regulation in normal cells and in tumor cells of different origins. Despite the presence of numerous molecular biology tools, the sigma-2 receptor has managed to evade all cloning attempts to date. This project is directed at purification and identification of the sigma-2 receptor.